The overall objective of this research is to elucidate the relationship of delta-aminolevulinic acid (ALA) synthetase activity and the aging process. Hepatic ALA synthetase catalyzes the initial and rate-limiting step in heme biosynthesis and thus may control intracellular heme levels. As a result, the content of many heme proteins whose synthesis and degradation is regulated by heme, may also be affected by the activity of ALA synthetase. The consequences to the cell and organisms in ALA synthetase activity during senescence might be manifested as a lowered ability of microsomal P-450 to catalyze drug hydroxylations. Furthermore, the activity of hepatic ALA synthetase is increased several-fold by acute ethanol intoxication as well as by a variety of chemicals which also cause an experimental porphyria. ALA synthetase in control animals and the rate of its induction by ethanol and porphyrinogenic drugs will be compared in young, adult and senescent rats. The role of glucocorticoid hormones in potentiating the induction will be studied in aging animals. ALA synthetase will be purified sufficiently to permit an investigation at the molecular level of the mechanism by which ALA synthetase is controlled in hepatic mitochondria and to gain some understanding of both the "induction" of the enzyme and the age-related decreases in activity.